| Autor: |
Fon Tacer K; Center for Functional Genomics and Biochips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia., Kuzman D, Seliskar M, Pompon D, Rozman D |
| Jazyk: |
angličtina |
| Zdroj: |
Physiological genomics [Physiol Genomics] 2007 Oct 22; Vol. 31 (2), pp. 216-27. Date of Electronic Publication: 2007 Jun 12. |
| DOI: |
10.1152/physiolgenomics.00264.2006 |
| Abstrakt: |
The interaction between disrupted lipid homeostasis and immune response is implicated in the pathogenesis of several diseases, but the molecular bridges between the major players are still a matter of controversy. Our systemic study of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in the livers of mice exposed to 20-h cytokine/fasting for the first time shows that TNF-alpha interferes with adaptation to fasting and activates harmful proatherogenic pathways, partially through interaction with the insulin-Insig-sterol regulatory element binding protein (Srebp) signaling pathway. In addition to the increased expression of acute-phase inflammatory genes, the most prominent alterations represent modified lipid homeostasis observed on the gene expression and metabolite levels. These include reduction of HDL-cholesterol, increase of LDL-cholesterol, and elevated expression of cholesterogenic genes, accompanied by increase of potentially harmful precholesterol metabolites and suppression of cholesterol elimination through bile acids, likely by farnesoid X receptor-independent mechanisms. On the transcriptional level, a shift from fatty oxidation toward fatty acid synthesis is observed. The concept of the influence of TNF-alpha on the Srebp regulatory network, followed by downstream effects on sterol metabolism, is novel. Observed acute alterations in lipid metabolism are in agreement with chronic disturbances found in patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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